Utilization of Rad51C promoter for transcriptional targeting of cancer cells
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Yan Cao1,*, Yan Xu1,*, Lei Zhang1,*, Zhen Li1, Ying Jiang1, Xiao Tian2, Andrei Seluanov2, Vera Gorbunova2, and Zhiyong Mao1
1. School of Life Sciences and Technology, Tongji University, Shanghai, China
2. Department of Biology, University of Rochester, Rochester, NY, USA
* These authors contributed equally to the work
Vera Gorbunova, email:
Zhiyong Mao, email:
Keywords: Rad51C promoter, Rad51 paralogs, cancer therapy, DNA double strand break repair, homologous recombination
Received: January 12, 2014 Accepted: February 18, 2014 Published: February 19, 2014
Cancer therapy that specifically targets malignant cells with minimal or no toxicity to normal tissue has been a long-standing goal of cancer research. Rad51 expression is elevated in a wide range of cancers and Rad51 promoter has been used to transcriptionally target tumor cells, however, a large size of Rad51 promoter limits its application for gene therapy. To identify novel tumor-specific promoters, we examined expression levels of Rad51 paralogs, Rad51B, Rad51C, and Rad51D as well as Rad52 in a panel of normal and tumor cell lines. We found that Rad51C is significantly overexpressed in cancer cells. The expression was up-regulated by approximately 6-fold at the mRNA level and 9-fold at the protein level. Interestingly, the 2064 bp long Rad51C promoter fragment was approximately 300-fold higher in cancer cells than in normal cells. A construct containing Rad51C promoter driving diphtheria toxin A efficiently killed several types of cancer cells with very mild effect to normal cells. These results underscore the potential of targeting the homologous recombination pathway in cancer cells and provide a proof of principle that the Rad51C promoter fragment can be used to transcriptionally target cancer cells.
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